chr20-3889109-G-A

Variant names:

• chr20-3889109-G-A
• rs1211425299
• ENST00000316562.9:c.9G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_153638.4(PANK2):​c.9G>A​(p.Arg3Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R3R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PANK2 NM_153638.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.281
• Publications: 0 publications found

Genes affected

PANK2 (HGNC:15894): (pantothenate kinase 2) This gene encodes a protein belonging to the pantothenate kinase family and is the only member of that family to be expressed in mitochondria. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by acyl CoA species. Mutations in this gene are associated with HARP syndrome and pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden-Spatz syndrome. Alternative splicing, involving the use of alternate first exons, results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-3889109-G-A is Benign according to our data. Variant chr20-3889109-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2879180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.281 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153638.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK2	NM_153638.4		c.9G>A	p.Arg3Arg	synonymous	Exon 1 of 7	NP_705902.2	Q9BZ23-1
	PANK2	NM_001324192.1		c.9G>A	p.Arg3Arg	synonymous	Exon 1 of 2	NP_001311121.1
	PANK2	NM_024960.6		c.-246+205G>A		intron	N/A	NP_079236.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK2	ENST00000316562.9	TSL:1	c.9G>A	p.Arg3Arg	synonymous	Exon 1 of 7	ENSP00000313377.4	Q9BZ23-1
	PANK2	ENST00000497424.5	TSL:2	c.-246+205G>A		intron	N/A	ENSP00000417609.1	Q9BZ23-2
	PANK2	ENST00000495692.5	TSL:3	c.-538+93G>A		intron	N/A	ENSP00000476745.1	V9GYH1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000664 AC: 1 AN: 150662 AF XY: 0.0000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000233

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394310 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 687410

African (AFR) AF: 0.00 AC: 0 AN: 31544

American (AMR) AF: 0.00 AC: 0 AN: 35606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24878

East Asian (EAS) AF: 0.00 AC: 0 AN: 35748

South Asian (SAS) AF: 0.00 AC: 0 AN: 78966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076762

Other (OTH) AF: 0.0000173 AC: 1 AN: 57718

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Pigmentary pallidal degeneration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.3
DANN	Benign	0.73
PhyloP100		0.28
PromoterAI		-0.021	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1211425299; hg19: chr20-3869756;